Development and Characterization of Nano-Sized Emulsion Systems Incorporated Polyphenolic Compound for Application Through the Skin
Yıl: 2022 Cilt: 47 Sayı: 1 Sayfa Aralığı: 57 - 72 Metin Dili: İngilizce DOI: 10.55262/fabadeczacilik.1078888 İndeks Tarihi: 22-09-2022
Development and Characterization of Nano-Sized Emulsion Systems Incorporated Polyphenolic Compound for Application Through the Skin
Öz: In addition to having strong anti-oxidant properties, resveratrol has anti-cancer, anti-angiogenic, cardioprotective, anti-diabetic, antiviral, and neuroprotective activities. Despite its rapid absorption, first-pass effect and intestinal metabolism reduce the bioavailability of resveratrol. Moreover, the lipophilic property of resveratrol reduces its water solubility and metabolized in high incidence reduces its oral bioavailability. Therefore, it was aimed to develop an optimum formulation for the skin application of resveratrol to overcome the negatives after oral administration.Since their easy formulation, thermodynamically stable properties, and facilitating the delivery of both lipophilic and hydrophilic active ingredients, loading resveratrol to microemulsions (MEs) will be a suitable delivery system to overcome the drawback of stability problems and skin bioavailability of resveratrol. A Triangle phase diagram was constructed, and the MEs region was determined by points studies. Subsequently, some formulations were selected within the transparent region by considering characteristics required to achieve optimized transdermal drug delivery. Chosen formulations were exposed to pre-stability tests such as centrifuge and thermal stress tests. Characterization studies such as droplet size, size distribution, zeta potential, viscosity, pH measurement were performed on remained intact formulations after pre-stability tests. In terms of the characterization test results such as pH, viscosity, conductivity, there wasn’t found significant difference observed between formulations. However, polydispersity index and zeta potential values provided to choosing optimal formulation.
Anahtar Kelime: Deriden Uygulama İçin Polifenolik Bileşik İçeren Nano Boyutlu Emülsiyon Sistemlerinin Geliştirilmesi ve Karakterizasyonu
Öz: Resveratrol güçlü bir antioksidan özelliğe sahip olmasının yanı sıra anti- kanser, anti-anjiyojenik, kardiyoprotektif, anti-diyabetik, anti-viral ve nöroprotektif aktivitelere sahiptir. İnsan vücudunda hızlı emilime uğramasına rağmen, bağırsak ve karaciğer metabolizması, resveratrolün sistemik biyoyararlanımı için hız sınırlayıcıdırlar. Ayrıca, resveratrolün yüksek lipofilikliği, suda çözünürlüğünü ve oral yoldan yüksek oranda metabolize edilmesi nedeni ile oral biyoyararlanımını azaltır. Bu nedenle, oral uygulama ile görülen olumsuzlukların üstesinden gelmek için resveratrolün deri uygulaması için optimum bir formülasyon geliştirilmesi amaçlanmıştır.Kolay formüle edilebilmeleri, termodinamik olarak kararlı olmaları ve hem lipofilik hem de hidrofilik etkin maddelerin vücuda verilmesini kolaylaştırmalarından dolayı, resveratrolün mikroemülsiyonlara (ME’ler) yüklenmesi, stabilite sorunları ve deriden emiliminin zor olması gibi dezavantajlarının üstesinden gelmek için uygun bir ilaç taşıyıcı sistemi olacaktır.Bu çalışmada önce üçgen faz diyagramı oluşturularak MEs bölgesi noktasal çalışma ile belirlendi. Daha sonra optimize edilmiş formülasyonu elde etmek için gerekli özellikler göz önünde bulundurularak ME sistemleri oluşturan bölge içinde bazı formülasyonları seçildi. Seçilen formülasyonlar, santrifüj ve termal stres testleri gibi ön stabilite testlerine tabi tutuldu. Damlacık boyutu, damlacık boyut dağılımı, zeta potansiyeli, viskozite, pH ölçümü gibi karakterizasyon çalışmaları, ön stabilite testlerinden sonra fiziksel olarak bozulmadan kalan formülasyonlar üzerinde gerçekleştirildi. Viskozite, pH, iletkenlik gibi karakterizasyon testleri sonuçları açısından formülasyonlar transdermal uygulamalar için kabul edilebilir aralıktaydı. Ancak damlacık boyutu, polidispersite indeksi ve zeta potansiyel değerleri optimal formülasyonun belirlenmesini sağlamıştır.
Anahtar Kelime: Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
- Ambade, K. W., Jadhav, S. L., Gambhire, M. N., Kur- mi, S. D., Kadam, V. J., & Jadhav, K. R. (2008). Formulation and evaluation of flurbiprofen mi- croemulsion. Current Drug Delivery, 5(1), 32-41. doi:10.2174/156720108783331032
- Bakshi, P., Jiang, Y., Nakata, T., Akaki, J., Matsuoka, N., & Banga, A. K. (2018). Formulation Development and Characterization of Nanoemulsion-Based Formulation for Topical Delivery of Heparinoid. Journal of Pharmaceutical Science, 107(11), 2883- 2890. doi:10.1016/j.xphs.2018.07.015
- Balata, G. F., Essa, E. A., Shamardl, H. A., Zaidan, S. H., & Abourehab, M. A. S. (2016). Self-emulsi- fying drug delivery systems as a tool to improve solubility and bioavailability of resveratrol. Drug Design Development and Therapy, 10. doi:10.2147/ Dddt.S95905
- Baur, J. A., Pearson, K. J., Price, N. L., Jamieson, H. A., Lerin, C., Kalra, A., . . . Sinclair, D. A. (2006). Res- veratrol improves health and survival of mice on a high-calorie diet. Nature, 444(7117), 337-342. doi:10.1038/nature05354
- Baur, J. A., & Sinclair, D. A. (2006). Therapeutic poten- tial of resveratrol: the in vivo evidence. Nature Re- views Drug Discovery , 5(6), 493-506. doi:10.1038/ nrd2060
- Baxter, R. A. (2008). Anti-aging properties of res- veratrol: review and report of a potent new an- tioxidant skin care formulation. Journal of Cos- metic Dermatology, 7(1), 2-7. doi:10.1111/j.1473- 2165.2008.00354.x
- Bayrak, Y., & Iscan, M. (2005). Studies on the phase behavior of the system non-ionic surfactant/alco- hol/alkane/H2O. Colloids and Surfaces a-Physico- chemical and Engineering Aspects, 268(1-3), 99- 103. doi:10.1016/j.colsurfa.2005.06.021
- Benson, H. A. (2012). Skin structure, function, and permeation. Topical and Transdermal Drug Deliv- ery: Principles and Practice, 1st ed.; Benson, HAE, Watkinson, AC, Eds, 1-22.
- Carter, P., Narasimhan, B., & Wang, Q. (2019). Bio- compatible nanoparticles and vesicular systems in transdermal drug delivery for various skin diseas- es. International Journal of Pharmaceutics , 555, 49-62. doi:10.1016/j.ijpharm.2018.11.032
- Chen, Y., Zhang, H., Yang, J., & Sun, H. (2015). Im- proved antioxidant capacity of optimization of a self-microemulsifying drug delivery system for resveratrol. Molecules, 20(12), 21167-21177.
- Cho, Y. H., Kim, S., Bae, E. K., Mok, C., & Park, J. (2008). Formulation of a cosurfactant free o/w microemulsion using nonionic surfactant mix- tures. Journal of Food Science, 73(3), E115-E121.
- Cicero, N., Albergamo, A., Salvo, A., Bua, G. D., Bar- tolomeo, G., Mangano, V., . . . Dugo, G. (2018). Chemical characterization of a variety of cold- pressed gourmet oils available on the Brazilian market. Food Research International, 109, 517-525. doi:10.1016/j.foodres.2018.04.064
- Constantinides, P. P. (1995). Lipid microemulsions for improving drug dissolution and oral absorption: physical and biopharmaceutical aspects. Pharma- ceutical Research, 12(11), 1561-1572.
- Danaei, M., Dehghankhold, M., Ataei, S., Hasanzadeh Davarani, F., Javanmard, R., Dokhani, A., . . . Mo- zafari, M. R. (2018). Impact of Particle Size and Polydispersity Index on the Clinical Applications of Lipidic Nanocarrier Systems. Pharmaceutics, 10(2). doi:10.3390/pharmaceutics10020057
- Das, S., Chaudhury, A., & Ng, K.-Y. (2011). Polyeth- yleneimine-modified pectin beads for colon-specif- ic drug delivery: In vitro and in vivo implications. Journal of Microencapsulation, 28(4), 268-279.
- Das, S., Lee, S. H., Chow, P. S., & Macbeath, C. (2020). Microemulsion composed of combination of skin beneficial oils as vehicle: Development of resver- atrol-loaded microemulsion based formulations for skin care applications. Colloids and Surfaces B: Biointerfaces, 194, 111161.
- Das, S., Lin, H. S., Ho, P. C., & Ng, K. Y. (2008). The impact of aqueous solubility and dose on the pharmacokinetic profiles of resveratrol. Pharma- ceutical Research, 25(11), 2593-2600. doi:10.1007/ s11095-008-9677-1
- Das, S., & Ng, K. Y. (2010a). Colon-specific delivery of resveratrol: optimization of multi-particulate calcium-pectinate carrier. International Journal of Pharmacology, 385(1-2), 20-28. doi:10.1016/j. ijpharm.2009.10.016
- Das, S., & Ng, K. Y. (2010b). Impact of glutaraldehyde on in vivo colon-specific release of resveratrol from biodegradable pectin-based formulation. Journal of Pharmaceutical Sciences, 99(12), 4903- 4916. doi:10.1002/jps.22212
- Das, S., & Ng, K. Y. (2010c). Resveratrol-loaded cal- cium-pectinate beads: effects of formulation pa- rameters on drug release and bead characteristics. Journal of Pharmaceutical Sciences, 99(2), 840- 860. doi:10.1002/jps.21880
- Das, S., Ng, K. Y., & Ho, P. C. (2010). Formulation and optimization of zinc-pectinate beads for the con- trolled delivery of resveratrol. AAPS PharmSciTech, 11(2), 729-742. doi:10.1208/s12249-010-9435-7
- Davidov-Pardo, G., & McClements, D. J. (2014). Res- veratrol encapsulation: Designing delivery sys- tems to overcome solubility, stability and bioavail- ability issues. Trends in Food Science & Technology, 38(2), 88-103. doi:10.1016/j.tifs.2014.05.003
- Delmas, D., Lancon, A., Colin, D., Jannin, B., & La- truffe, N. (2006). Resveratrol as a chemopreven- tive agent: A promising molecule for fighting can- cer. Current Drug Targets, 7(4), 423-442. doi:Doi 10.2174/138945006776359331
- Djekic, L., & Primorac, M. (2008). The influence of cosurfactants and oils on the formation of phar- maceutical microemulsions based on PEG-8 ca- prylic/capric glycerides. International Journal of Pharmaceutics, 352(1-2), 231-239.
- El Maghraby, G. M. (2008). Transdermal delivery of hydrocortisone from eucalyptus oil microemul- sion: effects of cosurfactants. International Journal of Pharmaceutics, 355(1-2), 285-292.
- Figueiredo, K. A., Neves, J. K. O., da Silva, J. A., de Freitas, R. M., & Carvalho, A. L. M. (2016). Phe- nobarbital loaded microemulsion: development, kinetic release and quality control. Brazilian Jour- nal of Pharmaceutical Sciences, 52(2), 251-263. doi:10.1590/S1984-82502016000200003
- Fisher, G. J., Wang, Z. Q., Datta, S. C., Varani, J., Kang, S., & Voorhees, J. J. (1997). Pathophysiology of premature skin aging induced by ultraviolet light. New England Journal of Medicine, 337(20), 1419- 1428. doi:10.1056/NEJM199711133372003
- Flanagan, J., & Singh, H. (2006). Microemulsions: a potential delivery system for bioactives in food. Critical Reviews in Food Science and Nutrition, 46(3), 221-237.
- Francioso, A., Mastromarino, P., Restignoli, R., Boffi, A., d’Erme, M., & Mosca, L. (2014). Improved sta- bility of trans-resveratrol in aqueous solutions by carboxymethylated (1,3/1,6)-beta-D-glucan. The Journal of Agricultural and Food Chemistry, 62(7), 1520-1525. doi:10.1021/jf404155e
- Gallarate, M., Carlotti, M. E., Trotta, M., Grande, A., & Talarico, C. (2004). Photostability of naturally oc- curring whitening agents in cosmetic microemul- sions. Journal of Cosmetic Science, 55(2), 139-148.
- Ganta, S., Talekar, M., Singh, A., Coleman, T. P., & Amiji, M. M. (2014). Nanoemulsions in Transla- tional Research-Opportunities and Challenges in Targeted Cancer Therapy. AAPS PharmSciTech, 15(3), 694-708. doi:10.1208/s12249-014-0088-9
- Gorini, I., Iorio, S., Ciliberti, R., Licata, M., & Armo- cida, G. (2019). Olive oil in pharmacological and cosmetic traditions. Journal of Cosmetic Dermatol- ogy, 18(5), 1575-1579.
- Hathout, R. M., Woodman, T. J., Mansour, S., Mor- tada, N. D., Geneidi, A. S., & Guy, R. H. (2010). Microemulsion formulations for the transdermal delivery of testosterone. European Journal of Phar- maceutical Sciences, 40(3), 188-196.
- Hegde, R. R., Verma, A., & Ghosh, A. (2013). Micro- emulsion: new insights into the ocular drug deliv- ery. International Scholarly Research Notices, 2013.
- Heuschkel, S., Goebel, A., & Neubert, R. H. (2008). Microemulsions—modern colloidal carrier for dermal and transdermal drug delivery. Journal of Pharmaceutical Sciences, 97(2), 603-631.
- Ibrahim, T. M., Abdallah, M. H., El-Megrab, N. A., & El-Nahas, H. M. (2018). Upgrading of dissolu- tion and anti-hypertensive effect of Carvedilol via two combined approaches: self-emulsification and liquisolid techniques. Drug Development and In- dustrial Pharmacy , 44(6), 873-885. doi:10.1080/0 3639045.2017.1417421
- Jang, M., Cai, L., Udeani, G. O., Slowing, K. V., Thomas, C. F., Beecher, C. W., . . . Pezzuto, J. M. (1997). Cancer chemopreventive activity of res- veratrol, a natural product derived from grapes. Science, 275(5297), 218-220. doi:10.1126/sci- ence.275.5297.218
- Juškaitė, V., Ramanauskienė, K., & Briedis, V. (2015). De- sign and formulation of optimized microemulsions for dermal delivery of resveratrol. Evidence-Based Complementary and Alternative Medicine, 2015.
- Kaur, R., & Ajitha, M. (2019). Transdermal delivery of fluvastatin loaded nanoemulsion gel: Preparation, characterization and in vivo anti-osteoporosis ac- tivity. European Journal of Pharmaceutical Scienc- es, 136, 104956. doi:10.1016/j.ejps.2019.104956
- Kreilgaard, M. (2002). Influence of microemulsions on cutaneous drug delivery. Advanced Drug De- livery Reviews, 54 Suppl 1, S77-98. doi:10.1016/ s0169-409x(02)00116-3
- Kural, F. H., & Gürsoy, R. N. (2011). Formulation and Characterization of Surfactin-Containing Self-Microemulsifying Drug Delivery Systems SF-SMEDDS. Hacettepe Üniversitesi Eczacılık Fakültesi Dergisi(2), 171-186.
- Lane, M. E. (2013). Skin penetration enhancers. In- ternational Journal of Pharmaceutics, 447(1-2), 12-21.
- Langcake, P., & Pryce, R. (1976). The production of resveratrol by Vitis vinifera and other members of the Vitaceae as a response to infection or injury. Physiological Plant Pathology, 9(1), 77-86.
- Lawrence, M. J. (1994). Surfactant systems: micro- emulsions and vesicles as vehicles for drug de- livery. European Journal of Drug Metabolism and Pharmacokinetics, 19(3), 257-269.
- Lawrence, M. J., & Rees, G. D. (2000). Microemul- sion-based media as novel drug delivery systems. Advanced Drug Delivery Reviews, 45(1), 89-121.
- Lawrence, M. J., & Rees, G. D. (2012). Microemul- sion-based media as novel drug delivery systems. Advanced Drug Delivery Reviews, 64, 175-193. doi:10.1016/j.addr.2012.09.018
- Lemerya, E., Briancon, S., Chevalier, Y., Bordes, C., Oddos, T., Gohier, A., & Bolzinger, M. A. (2015). Skin toxicity of surfactants: Structure/toxicity relationships. Colloids and Surfaces a-Physico- chemical and Engineering Aspects, 469, 166-179. doi:10.1016/j.colsurfa.2015.01.019
- Liu, C. H., & Chang, F. Y. (2011). Development and characterization of eucalyptol microemulsions for topic delivery of curcumin. Chemical and Pharmaceutical Bulletin(Tokyo), 59(2), 172-178. doi:10.1248/cpb.59.172
- Mahapatra, A. K., Murthy, P. N., Swadeep, B., & Swain, R. (2014). Self-emulsifying drug delivery systems (SEDDS): An update from formulation develop- ment to therapeutic strategies. International Jour- nal of PharmTech Research, 6(2), 546-568.
- Malcolmson, C., & Lawrence, M. J. (1993). A compar- ison of the incorporation of model steroids into non-ionic micellar and microemulsion systems. Journal of Pharmacy and Pharmacology, 45(2), 141-143.
- Malcolmson, C., & Lawrence, M. J. (1995). Three-com- ponent non-ionic oil-in-water microemulsions using polyoxyethylene ether surfactants. Colloids and surfaces B: Biointerfaces, 4(2), 97-109.
- Mukhopadhyay, P., Mukherjee, S., Ahsan, K., Bagchi, A., Pacher, P., & Das, D. K. (2010). Restoration of altered microRNA expression in the ischemic heart with resveratrol. Plos One, 5(12), e15705.
- Ndiaye, M., Philippe, C., Mukhtar, H., & Ahmad, N. (2011). The grape antioxidant resveratrol for skin disorders: promise, prospects, and challenges. Ar- chives of Biochemistry and Biophysics , 508(2), 164- 170. doi:10.1016/j.abb.2010.12.030
- Nguyen, S. H., Dang, T. P., & Maibach, H. I. (2007). Comedogenicity in rabbit: some cosmetic ingre- dients/vehicles. Cutaneous and ocular toxicology, 26(4), 287-292.
- Parmar, K., Patel, J., & Sheth, N. (2015). Self na- no-emulsifying drug delivery system for Embe- lin: Design, characterization and in-vitro studies. Asian Journal of Pharmaceutical Sciences, 10(5), 396-404. doi:10.1016/j.ajps.2015.04.006
- Patel, M. R., Patel, R. B., Parikh, J. R., Solanki, A. B., & Patel, B. G. (2009). Effect of formulation com- ponents on the in vitro permeation of micro- emulsion drug delivery system of fluconazole. AAPS PharmSciTech, 10(3), 917-923. doi:10.1208/ s12249-009-9286-2
- Patravale, V. B., & Mandawgade, S. D. (2008). Novel cosmetic delivery systems: an application update. International Journal of Cosmetic Science, 30(1), 19-33. doi:10.1111/j.1468-2494.2008.00416.x
- Perazzo, A., Preziosi, V., & Guido, S. (2015). Phase inversion emulsification: Current understand- ing and applications. Advances in Colloid and Interface Science, 222, 581-599. doi:10.1016/j. cis.2015.01.001
- Rani, S., Rana, R., Saraogi, G. K., Kumar, V., & Gupta, U. (2019). Self-Emulsifying Oral Lipid Drug De- livery Systems: Advances and Challenges. AAPS PharmSciTech, 20(3), 129. doi:10.1208/s12249- 019-1335-x
- Rastogi, V., & Yadav, P. (2014). Transdermal drug de- livery system: An overview. Asian Journal of Phar- maceutics, 6(3), 161-170.
- Salimi, A., Sharif Makhmal Zadeh, B., & Moghimipo- ur, E. (2013). Preparation and characterization of cyanocobalamin (vit B12) microemulsion prop- erties and structure for topical and transdermal application. Iranian Journal of Basic Medical Sci- ences, 16(7), 865-872.
- Saribey, G., Kahraman, E., ERDAL, M., & GÜNGÖR, S. (2021). Design and characterisation of colloi- dal nanocarriers for enhanced skin delivery of etodolac. Journal of Research in Pharmacy, 25(1), https://doi.org/10.35333/jrp.2021.289
- Sessa, M., Tsao, R., Liu, R., Ferrari, G., & Donsì, F. (2011). Evaluation of the stability and antioxidant activity of nanoencapsulated resveratrol during in vitro digestion. Journal of Agricultural and Food Chemistry, 59(23), 12352-12360.
- Shah, N., Carvajal, M., Patel, C., Infeld, M., & Malick, A. (1994). Self-emulsifying drug delivery systems (SEDDS) with polyglycolyzed glycerides for im- proving in vitro dissolution and oral absorption of lipophilic drugs. International Journal of Pharma- ceutics, 106(1), 15-23.
- Sharma, S., Shukla, P., Misra, A., & Mishra, P. R. (2014). Interfacial and colloidal properties of emulsified systems: pharmaceutical and biological perspective. In Colloid and interface science in pharmaceutical research and development (pp. 149-172): Elsevier.
- Sheshala, R., Anuar, N. K., Abu Samah, N. H., & Wong, T. W. (2019). In Vitro Drug Dissolution/ Permeation Testing of Nanocarriers for Skin Application: a Comprehensive Review. AAPS PharmSciTech, 20(5), 164. doi:10.1208/s12249- 019-1362-7
- Singh, M. K., Chandel, V., Gupta, V., & Ramteke, S. (2010). Formulation development and character- ization of microemulsion for topical delivery of Glipizide. Der Pharmacia Lettre, 2(3), 33-42.
- Solans, C., Morales, D., & Homs, M. (2016). Sponta- neous emulsification. Current Opinion in Colloid & Interface Science, 22, 88-93.
- Surber, C., & Kottner, J. (2017). Skin care products: What do they promise, what do they deliver. Jour- nal of Tissue Viability, 26(1), 29-36. doi:10.1016/j. jtv.2016.03.006
- Syed, H. K., & Peh, K. K. (2014). Identification of Phases of Various Oil, Surfactant/Co-Surfactants and Water System by Ternary Phase Diagram. Acta Poloniae Pharmaceutica, 71(2), 301-309.
- Tenjarla, S. (1999). Microemulsions: an overview and pharmaceutical applications. Critical Reviews™ in Therapeutic Drug Carrier Systems, 16(5).
- Thakkar, P. J., Madan, P., & Lin, S. S. (2014). Trans- dermal delivery of diclofenac using water-in-oil microemulsion: formulation and mechanistic approach of drug skin permeation. Pharmaceuti- cal Development and Technology, 19(3), 373-384. doi:10.3109/10837450.2013.788658
- Trommer, H., & Neubert, R. H. (2006). Overcoming the stratum corneum: the modulation of skin pen- etration. A review. Skin Pharmacology and Physi- ology, 19(2), 106-121. doi:10.1159/000091978
- Ujilestari, T., Dono, N. D., Ariyadi, B., Martien, R., & Zuprizal. (2018). Formulation and characteriza- tion of self-nano emulsifying drug delivery sys- tems of lemongrass (cymbopogon citratus) essen- tial oil. Malaysian Journal of Fundamental and Ap- plied Sciences, 14(3), 360-363. doi:DOI 10.11113/ mjfas.v14n3.1070
- Umerska, A., Cassisa, V., Matougui, N., Joly-Guillou, M. L., Eveillard, M., & Saulnier, P. (2016). Antibac- terial action of lipid nanocapsules containing fatty acids or monoglycerides as co-surfactants. Euro- pean Journal of Pharmaceutics and Biopharmaceu- tics, 108, 100-110. doi:10.1016/j.ejpb.2016.09.001
- Van Staden, D., Du Plessis, J., & Viljoen, J. (2020). De- velopment of a self-emulsifying drug delivery sys- tem for optimized topical delivery of clofazimine. Pharmaceutics, 12(6), 523.
- van Zyl, L., du Preez, J., Gerber, M., du Plessis, J., & Viljoen, J. (2016). Essential Fatty Acids as Trans- dermal Penetration Enhancers. Journal of Pharma- ceutical Sciences, 105(1), 188-193. doi:10.1016/j. xphs.2015.11.032
- Walle, T., Hsieh, F., DeLegge, M. H., Oatis, J. E., & Walle, U. K. (2004). High absorption but very low bioavailability of oral resveratrol in humans. Drug Metabolism and Disposition, 32(12), 1377-1382.
- Warisnoicharoen, W., Lansley, A., & Lawrence, M. (2000). Nonionic oil-in-water microemulsions: the effect of oil type on phase behaviour. Interna- tional Journal of Pharmaceutics, 198(1), 7-27.
- Zaichik, S., Steinbring, C., Menzel, C., Knabl, L., Orth-Holler, D., Ellemunter, H., ... Bern- kop-Schnurch, A. (2018). Development of self-emulsifying drug delivery systems (SEDDS) for ciprofloxacin with improved mucus perme- ating properties. International Journal of Phar- macology, 547(1-2), 282-290. doi:10.1016/j.ij- pharm.2018.06.005
- Zhang, L., Zhang, L., Zhang, M., Pang, Y., Li, Z., Zhao, A., & Feng, J. (2015). Self-emulsifying drug deliv- ery system and the applications in herbal drugs. Drug Delivery, 22(4), 475-486. doi:10.3109/10717 544.2013.861659
- Zillich, O. V., Schweiggert-Weisz, U., Eisner, P., & Ker- scher, M. (2015). Polyphenols as active ingredi- ents for cosmetic products. International Journal of Cosmetic Science, 37(5), 455-464. doi:10.1111/ ics.12218
| APA | Samancı B, Yener G, Degim I (2022). Development and Characterization of Nano-Sized Emulsion Systems Incorporated Polyphenolic Compound for Application Through the Skin. , 57 - 72. 10.55262/fabadeczacilik.1078888 |
| Chicago | Samancı Bülent,Yener Gülgün,Degim Ismail Tuncer Development and Characterization of Nano-Sized Emulsion Systems Incorporated Polyphenolic Compound for Application Through the Skin. (2022): 57 - 72. 10.55262/fabadeczacilik.1078888 |
| MLA | Samancı Bülent,Yener Gülgün,Degim Ismail Tuncer Development and Characterization of Nano-Sized Emulsion Systems Incorporated Polyphenolic Compound for Application Through the Skin. , 2022, ss.57 - 72. 10.55262/fabadeczacilik.1078888 |
| AMA | Samancı B,Yener G,Degim I Development and Characterization of Nano-Sized Emulsion Systems Incorporated Polyphenolic Compound for Application Through the Skin. . 2022; 57 - 72. 10.55262/fabadeczacilik.1078888 |
| Vancouver | Samancı B,Yener G,Degim I Development and Characterization of Nano-Sized Emulsion Systems Incorporated Polyphenolic Compound for Application Through the Skin. . 2022; 57 - 72. 10.55262/fabadeczacilik.1078888 |
| IEEE | Samancı B,Yener G,Degim I "Development and Characterization of Nano-Sized Emulsion Systems Incorporated Polyphenolic Compound for Application Through the Skin." , ss.57 - 72, 2022. 10.55262/fabadeczacilik.1078888 |
| ISNAD | Samancı, Bülent vd. "Development and Characterization of Nano-Sized Emulsion Systems Incorporated Polyphenolic Compound for Application Through the Skin". (2022), 57-72. https://doi.org/10.55262/fabadeczacilik.1078888 |
| APA | Samancı B, Yener G, Degim I (2022). Development and Characterization of Nano-Sized Emulsion Systems Incorporated Polyphenolic Compound for Application Through the Skin. FABAD Journal of Pharmaceutical Sciences, 47(1), 57 - 72. 10.55262/fabadeczacilik.1078888 |
| Chicago | Samancı Bülent,Yener Gülgün,Degim Ismail Tuncer Development and Characterization of Nano-Sized Emulsion Systems Incorporated Polyphenolic Compound for Application Through the Skin. FABAD Journal of Pharmaceutical Sciences 47, no.1 (2022): 57 - 72. 10.55262/fabadeczacilik.1078888 |
| MLA | Samancı Bülent,Yener Gülgün,Degim Ismail Tuncer Development and Characterization of Nano-Sized Emulsion Systems Incorporated Polyphenolic Compound for Application Through the Skin. FABAD Journal of Pharmaceutical Sciences, vol.47, no.1, 2022, ss.57 - 72. 10.55262/fabadeczacilik.1078888 |
| AMA | Samancı B,Yener G,Degim I Development and Characterization of Nano-Sized Emulsion Systems Incorporated Polyphenolic Compound for Application Through the Skin. FABAD Journal of Pharmaceutical Sciences. 2022; 47(1): 57 - 72. 10.55262/fabadeczacilik.1078888 |
| Vancouver | Samancı B,Yener G,Degim I Development and Characterization of Nano-Sized Emulsion Systems Incorporated Polyphenolic Compound for Application Through the Skin. FABAD Journal of Pharmaceutical Sciences. 2022; 47(1): 57 - 72. 10.55262/fabadeczacilik.1078888 |
| IEEE | Samancı B,Yener G,Degim I "Development and Characterization of Nano-Sized Emulsion Systems Incorporated Polyphenolic Compound for Application Through the Skin." FABAD Journal of Pharmaceutical Sciences, 47, ss.57 - 72, 2022. 10.55262/fabadeczacilik.1078888 |
| ISNAD | Samancı, Bülent vd. "Development and Characterization of Nano-Sized Emulsion Systems Incorporated Polyphenolic Compound for Application Through the Skin". FABAD Journal of Pharmaceutical Sciences 47/1 (2022), 57-72. https://doi.org/10.55262/fabadeczacilik.1078888 |
